Genetic profiling and banking system and method

ABSTRACT

A genetic banking system allows the ability to securely store genetic profile data while allowing access to individuals authorized to access the profile for authorized purposes.

BACKGROUND OF THE INVENTION

[0001] This invention relates to a system for profiling and bankinggenetic information about individuals.

[0002] Genetic information derived from a sample can be used todetermine. medical and other information about an individual. Obtaininggenetic samples and testing those samples raises concerns about privacy,access, and the use of the resulting information. Such informationcould, however, be useful for individuals and medical practitioners.

[0003] Currently there are companies that provide banking services forstoring physical samples of genetic material from biological tissue,such as blood or cheek cells. That material can be retrieved fromstorage and tested as desired. Removing the sample and having it testedis time consuming and may be repetitive if multiple tests are neededover time.

SUMMARY OF THE INVENTION

[0004] The present invention includes systems and methods for storingand accessing genetic information. The systems and methods preferablyprovide protection against unauthorized access and use, but provideconvenience in accessing and using genetic information if such use isproperly authorized.

[0005] In a method according to the present invention, a patient enrollsin a genetic banking system and provides a source of genetic material,such as a blood sample. The sample is processed using a combination ofexperimental and/or in silico techniques to produce a genetic profilefor the patients. The processed data is stored in a database to create agenetic profile for that patient. A remaining portion of the physicalsample may also be stored for further use if needed.

[0006] The patient, either at the time of enrollment or after a sampleis processed, can dictate access rights, including the ability of thirdparties (other than the individual or the genetic bank itself), such asmedical practitioners, to access this profile, and the specific purposesfor which the profile can be accessed and used. Thus, the patient canspecify both the people who will have access, and the uses for whichthey have access.

[0007] The system provides user interfaces for the user to enteridentification information and access rights. The bank can preparestandard protocols that describe allowed and proscribed data sharing.

[0008] A medical practitioner authorized to have access by the patientand confirmed by the access control system can access the profile thatis stored and can run tests based on the profile as stored in thedatabase; for example, such a test can be run to determine the presenceor absence of certain markers.

[0009] In another aspect, a system according to the present inventionincludes a database for storing genetic data on individuals and anaccess control system that controls access to the database and managesthe tests that are to be done. The control system interacts with (orincludes) a testing system to cause the testing system to process theprofile data to conduct the desired test. The control system authorizesthe test and provides the results.

[0010] The system allows users to store a comprehensive digitized DNAprofile based on a sample, in addition to storage of physical samples.The patient has control to voluntarily allow access to particular peopleand for particular purposes, thus protecting the privacy of thatinformation. Because the samples have been processed and digitized,additional tests can be performed without requiring repetitive use ofactual physical samples. Other features and advantages will becomeapparent from the following description of preferred embodiments,drawings, and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011]FIG. 1 is a block diagram of a system according to the presentinvention.

[0012] FIGS. 2-4 are flow charts showing methods according to thepresent invention.

DESCRIPTION OF PREFERRED EMBODIMENTS

[0013] A genetic banking system 10 has a database 18 for storing geneticprofiles, and a processing system 12 for controlling interactionsbetween a patient 14 and database 18, and between a medical practitioner16 and database 18. System 10 may also include data integration andanalysis functionalities and a testing system 20 that is linked todatabase 18, and may also include physical storage 22 for storingphysical samples of genetic material. Processing system 12 maintainsaccess rights that allow a patient to specify and control the access tothe profile by others such as medical practitioners, enforces the accessrights that are voluntarily provided from the patient, causes testingsystem 20 to perform a desired test, and provides results to the medicalpractitioner.

[0014] Database 18 may be a relational database with a relationaldatabase management system (RDBMS), or it may use technology such asthat in ACEDB, a genome database system that has a custom databasekernel, a data model designed specifically for handling scientific dataflexibly, and a graphical user interface with many specific displays andtools for genomic data. ACEDB software and supporting tools are publiclyavailable via the Internet by download.

[0015] Processing system 12 and the testing system 20 may each include aspecial purpose computer, a workstation, a server, or some combinationof linked computers, workstations, and/or servers for interfacing withusers, processing, information and performing tests. The connectionsemployed are preferably high speed, TCP/IP connections, such as T1lines. The testing system may be independent and remote from processingsystem 12 that interacts with users and medical practitioners, or thetesting system and processing system may be part of one largerprocessing system.

[0016] Referring to the flow chart of FIG. 2, a source of geneticmaterial, such as a blood sample, is provided by a patient for testingpurposes after the patient enrolls with the system (100). Thisenrollment process includes the processing system providing a userinterface to the patient, and the patient providing information abouthimself/herself through the user interface to the processing systemabout himself/herself. The patient, using the user interface,voluntarily establishes conditions under which the genetic informationcan be accessed, preferably through use of a menu of standard proptocolsor by selecting a standard protocol and customizing it. The patient canthus determine access rights, including both who gets access and theuses that can be made of that genetic information. Thus, at least someauthorized third parties users may have access for some purposes and notfor other purposes, or some third parties may have access rights set to“all” for all purposes.

[0017] To confirm selections regarding access and use made by thepatients, the system preferably employs a process of querying andconfirming through the user interface, and preferably also includesinformation for the patient about the system and about the tests.Redundancies and checks can be provided in the interaction between thepatient and the user interface during the enrollment process so that thepatient understands the possible uses of the profile and theconsequences of selecting who gets access and the uses for that access.

[0018] To enroll, the patient preferably either obtains from theprocessing system a password at the time of enrollment, or the patientmay have previously been provided with a password for confidentiality.The system preferably provides a high level of security and may includemechanisms such as digital certificates in addition to the passwordprotection. The enrollment can take place on a private or other closedor dedicated network, such as a LAN or Intranet, or with appropriatesecurity measures, over the Internet, and can be performed withoutadditional human intervention (i.e., additional to the user). ForInternet interaction, the processing system can include a web server forproviding pages or forms and for receiving information entered ontothose forms.

[0019] When the patient is enrolled, the patient has a physical sourceof genetic material shipped to the genetic banking system or some otherdesired location for processing (102).

[0020] At a later time, the patient can use the password or a newpassword to change selections for who can get access and the uses forwhich access can be made. In addition, the selections can “time out”such that the user must re-confirm selections after some period of timeor else the access rights are terminated.

[0021] The physical sample is processed by the testing system and theresults of the processing are stored in the database. The processingthat is performed on the sample can vary depending on the geneticbanking and testing services that are provided, but can includegenotyping and bioinformatic profiling of general and/or specificgenetic marker panels. Such information can be used to determine risksof many diseases including, without limitation, cancer, Huntington'sDisease, Alzheimer's Disease, and hypertension. The tests can be donethrough a number of different methods, such as fluorescence, opticaldensity, mass spectroscopy, DNA sequencing, microarray-based assays, orother current methods or methods to be developed. The data that isprovided from these tests is digitally stored in the database as agenetic profile of the patient for subsequent analysis and tests.

[0022] After the tests are done, the actual physical sample (or at leastany remaining portion) may be stored if desired in case it is needed forconfirmation or other future purposes (106). This physical storage canbe done using known cryogenic techniques.

[0023] Referring to FIG. 3, a third party, such as a medicalpractitioner (i.e., a party other than the patient or people associatedwith the management and/or operation of the genetic banking system), mayseek access to an enrolled individual's profile in the database (110)using a user interface provided from the processing system to thepractitioner. The practitioner is authenticated, such as through the useof digital certificates and/or password protection before he/she canaccess the information. The system compares the access rights entered bythe patient into the system with that third party practitioner seekingaccess to the patient's profile. The system then determines whetheraccess is allowed for that third party practitioner (112).

[0024] If the access is allowed, the practitioner can seek to have atest performed, such as a search of the profile for markers forHuntington's Disease (114). The system determines whether the test isauthorized by comparing the type of test that is desired with the accessrights entered by the patient (116) (a paractitioner may have access forsome purposes but not others). If the test is authorized, the processingsystem forwards the request to the testing system to perform the test.The results of the test can be analyzed in the processing system ifneeded and provided to the practitioner, preferably in an encrypted form(118). The connections that are provided, particularly between database18 and testing system 20, should have high bandwidth to allow asignificant amount of data to be quickly provided to the testing systemfor the results. Testing system 20 should be sufficientlycomputationally intensive in order to perform the requested tests.

[0025] If access by the practitioner is not allowed, or if theparticular test is not authorized, the patient can log in to the systemto provide the appropriate authorizations for access (120, 122).

[0026] The practitioner can seek access over a dedicated or dosednetwork, or with appropriate security, over the Internet. The processesof seeking access, confirming access, performing the test, and reportingresults can all be performed without additional human intervention(other than the medical practitioner himself/herself).

[0027] The patient may or may not have access to have tests runindividually and without the tests being performed for a medicalpractitioner. It may be desirable for the patient only to have accessthrough a medical practitioner who can explain to the patient the actualmeaning of the tests. However, it would also be possible to allow thepatient to have tests performed and to have access to the results.

[0028] Referring to FIG. 4, a more detailed example of the sampleprocessing process is shown. In this process, the DNA is extracted fromthe sample, such as the blood sample (130). Extraction of DNA from asample of cells may be accomplished by any standard method. Using thepatient's DNA sample, a complete genotype (GT) and pan-loci ID areperformed (132). For example, a single nucleotide polymorphism (SNP) mapmay be generated from the patient's DNA sample. In the alternate, if thepatient has or is predisposed to develop a specific disease, genes(e.g., mutations, aberrant expression patterns) associated with thosediseases may be directly sequenced from the patient's sample. Next,high-throughput (HT) genotyping is executed (134). The results of thegenotyping data are provided in reports that are preferably customizedfor convenient use (136).

[0029] Several non-limiting genes, and the diseases with which they areassociated, which can be sequenced and/or from which a SNP map can begenerated according to the methods of the invention are provided inPulst S. M. (1999) Neurol. 56(6): 667-672; Ballantyne et al. (1997) J.Cardiovasc. Risk 4(5-6):353-356; Marian, A. J. (1997) J. Cardiovasc.Risk 4(5-6): 341-345; Marian, A. J. (1997) J. Cardiovasc. Risk 4(5-6):333-339; Hallman, D. M. et al. (1997) J. Cardiovasc. Risk 4(5-6):325-331; Ballantyne et al. (1997) J. Cardiovasc. Risk 4(5-6): 321-323.Additional genes the diseases with which they are associated are listedin Table I. TABLE I Gene Disease Reference* p53 cervical cancer Zehbe etal. (1999) Lancet 354(9174): 218-219 BRCA1 breast cancer Hakansson etal. (1997) Am. J. Hum. Genet. 60(5): 1068-1078 BRCA2 breast cancerHakansson et al. (1997) Am. J. Hum. Genet. 60(5): 1068-1078 CTLA-4thyroid Vaidya et al. (1999) Lancet 354 associated (9180): 743-744orbitopathy nitric oxide synthase coronary artery Liao et al. (1999)Angionlogy (eNOS) disease 50(8): 671-676 gene encoding Tangier diseaseRust et al. (1999) Nat. Genet. human ATP 22(4): 352-355, Brooks-Wilsoncassette-binding (1999) Nat. Genet. 22(4): 336-345 CTLA-4 multiplesclerosis Ligers et al. (1999) J. Neuro- immunol. 97(1-2): 182-190genetic marker multiple sclerosis Shinar et al. (1998) J. Mol. D6S461Neurosci. 11(3): 265-269 Microdeletions at Van der Woude Schutte et al.(1999) Am. J. chromosome bands syndrome Med. Genet. 84(2): 145-1501q32-q41 chromosome 21q22 bipolar affective Aita et al. (1999) Am. J.Hum. disorder Genet. 64(1): 210-217.

[0030] In addition to specific genes associated with specific diseases,many diseases are characterized by their association with a set of atleast one genetic marker which can be detected using the methods of thepresent invention. For example, a marker in the UCP-2/UCP-3 gene clusterhas been linked to a genetic susceptibility to anorexia nervosa(Campbell et al. (1999) Mol. Psychiatry 4(1): 68-70). Likewise, geneticmarkers in addition to apolipoprotein E (APOE) polymorphism has beenassociated with Alzheimer's disease (Scacchi et al. (1999) Neurosci.Lett. 259(1): 33-36). Parkinson's disease is similarly associated with acertain combined alpha-synuclein/apolipoprotein E genotype (Kruger etal. (1999) Ann. Neurol. 45(5): 611-617). The methods of the inventionmay also be employed to detect the presence of a multigeneic disease (orthe predisposition to develop such a disease) that is associated withand/or caused by the allelic variants of more than one gene.

[0031] For the purposes of the invention, it matters not whether thedisease is caused by and/or correlated with the associated geneticmarker or whether the associated genetic marker is caused by and/orcorrelated with the disease. What is relevant is that certain geneticmarkers, such as allelic variants, are associated with certain diseasephenotypes and/or predisposition to develop the disease.

[0032] The invention provides an accessible confidential database thatcreates and stores genetic information, such as an SNP map, from patientDNA. As more patient samples are added to the database of the invention,and as researchers find more associations between genetic markers andparticular disease phenotypes, use of the invention provides an on-goingself-perpetuating advancement into the development of associationsbetween genetic markers and certain diseases. Moreover, with appropriatesecurity and privacy cautions, the database can be used in an anonymousmanner to allow researchers to access a body of genetic information forresearch and analysis purposes.

[0033] The system of the present invention thus allows a patient tovoluntarily bank genetic information that can be used quickly todetermine genetic and medical information about that individual,particularly information that relates to whether the individual carriesgenetic information associated with known diseases. The system providesrestrictions, however, that allow the user to retain privacy and limitunauthorized access to his/her genetic information. The system is thusunlike a system, for example, in which DNA information, like fingerprintinformation, is stored for identification purposes to use DNAinformation to identify individuals involved in specific criminalactivities; in such a case, the individual who provides the sample wouldgenerally not have voluntary control to establish the ability of othersto access the information, and such systems would generally not have theability to test for a number of different medical purposes for which theDNA information can be accessed by others.

[0034] The patents and scientific literature referred to hereinestablish the knowledge of those with skill in the art and are herebyincorporated by reference in their entirety to the same extent as ifeach was specifically and individually indicated to be incorporated byreference. Any conflict between any reference cited herein and thespecific teachings of this specification shall be resolved in favor ofthe latter. Likewise, any conflict between an art-understood definitionof a word or phrase and a definition of the word or phrase asspecifically taught in this specification shall be resolved in favor ofthe latter.

[0035] Having described a preferred embodiment of the present invention,it should be apparent that modifications can be made without departingfrom the scope of the invention as defined by the appended claims. Forexample, the authorization is described as a two-step process ofchecking the user then the purpose, although the authorization couldcombine user and purpose into one combined access right. Whilecomponents of the preferred embodiment may have certain benefits andadvantages noted herein, other systems and components thereof maynonetheless be within the scope of the claims without necessarily havingeach and every one of the noted benefits and advantages.

What is claimed is:
 1. A method comprising: processing a user's physicalsample with genetic information to produce a profile of datarepresentative of the genetic information in the physical sample;storing the profile in an accessible database; receiving from the user aset of access rights defining conditions under which third party userscan access the profile; receiving a request from a third party user toaccess the profile to perform a test on the data; comparing the thirdparty user's request with the access rights to confirm that the thirdparty user is authorized to access the profile as requested; if thethird party user is authorized, performing the requested test on theprofile and reporting the results to the third party user; and if thethird party user is not authorized, denying access.
 2. The method ofclaim 1, wherein the access rights separately include users who can gainaccess and uses for which that access can be obtained, the comparingincluding comparing both that the third party user is allowed access andthat the third party user can perform the requested test.
 3. The methodof claim 1, wherein performing a requested test includes identifying inthe profile one of a number of genetic markers in the profile associatedwith certain disease phenotypes.
 4. The method of claim 1, whereinreceiving a request includes receiving a request over the Internet,wherein the receiving, comparing, performing, and reporting areperformed without additional human intervention.
 5. The method of claim1, further comprising providing to the user a user interface to allowthe user to enroll with the system to establish the access rights. 6.The method of claim 5, wherein the enrollment is performed over theInternet without additional human intervention.
 7. The method of claim1, wherein the processing includes performing one or more offluorescence, optical density, mass spectroscopy and DNA sequencing. 8.The method of claim 1, wherein performing a requested test includesidentifying in the profile one or more of the genes identified inTable
 1. 9. A method comprising: receiving over the Internet from athird party user a request to access a stored genetic profile of apatient to perform a medical test to determine the presence or absenceof a gene or marker associated with a specified disease; determiningwhether the third party user is authorized to access the profile for thepurpose of the requested medical test based on stored access rightsprovided by the patient; if the third party user is authorized foraccess and to perform the test, performing the test on the profile andreporting the results to the third party user requesting the testinformation; and if the third party user is not authorized for accessand to perform the test, denying access to the third party user and notperforming the test.
 10. The method of claim 9, further comprisingproviding to the user a user interface to allow the user to voluntarilyenter information to establish access rights.
 11. The method of claim10, wherein the entry of information is performed without additionalhuman interventions.
 12. The method of claim 9, wherein the accessrights include at least one third party that has rights to access theprofile for purposes of performing some medical tests and not forperforming other medical tests.
 13. The menthod of claim 9, whereinperforming the test includes determining whether a spceidic geneticmarker is present or not.
 14. The method of claim 9, wherein performingthe test includes determining whether a specific gene is present or not.15. A system comprising: a database for storing genetic profiles ofpatients; a testing system for performing medical tests on geneticprofiles; and a processing system: providing to the patient a userinterface for the patient to voluntarily enter information to establishaccess rights for authorizing access for third party users and purposesfor which the third party users can gain access, using the access rightsto control access to the database when access is requested by thirdparty users, in response to a request by a third party user for a teston the profile, checking the access rights to determine whether thethird party is authorized and whether the test is authorized, and, ifthe third party is authorized causing the testing system to perform thetest, and providing test results to the authorized entity.
 16. Thesystem of claim 15, wherein the profiles are stored in such a way thatone or more of a plurality of genetic markers associated with specificdiseases can be identified.
 17. The system of claim 15, wherein theprocessing system includes a web server for providing the user interfaceto the patient.
 18. The system of claim 15, wherein the processingsystem provides a third party interface to the third party for seekingaccess without additional human intervention.
 19. The system of claim15, wherein the genetic profiles include SNP maps.
 20. The system ofclaim 15, wherein the user can establish access rights and the thirdparty can try to obtain access all without additional humanintervention.